A CBT-based Mobile Intervention as First Line Treatment for Adolescent Depression During COVID-19

• ClinicalTrials.gov Identifier: NCT04524598
• Recruitment Status: Completed
• First Posted: August 24, 2020
• Results First Posted: December 13, 2021
• Last Update Posted: July 18, 2022
• Sponsor: Limbix Health, Inc.
• Information provided by (Responsible Party): Limbix Health, Inc.

Tracking Information

• First Submitted Date: August 20, 2020
• First Posted Date: August 24, 2020
• Results First Submitted Date: September 30, 2021
• Results First Posted Date: December 13, 2021
• Last Update Posted Date: July 18, 2022
• Actual Study Start Date: July 20, 2020
• Actual Primary Completion Date: September 3, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2021)

• Phase I - Feasibility (Eligibility) [ Time Frame: Pre-enrollment ]
  Descriptive report of participant eligibility. Percentage of people who enrolled in each arm after expressing interest in participating in the study. Phase I participant arms are reported for this outcome.
• Number of Participants With Willingness to Participate and Program Adherence [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Descriptive report of willingness to participate and program adherence. Phase I participant arms are reported for this outcome.
• Phase I - Feasibility (Satisfaction) [ Time Frame: Post-Treatment -"Week 5" ]
  Descriptive report of participant satisfaction (mood improvement and enjoyment) on a scale of 0-10, with 0 meaning lower satisfaction and 10 meaning higher satisfaction. Phase I participant arms are reported for this outcome.
• Phase I - Feasibility (Safety) [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Descriptive report of participant safety. Phase I participant arms are reported for this outcome.
• Phase II - Change in Depressive Symptoms [ Time Frame: Change from Baseline to Post treatment (5 weeks) ]
  Between-subjects treatment-related change in depressive symptoms from baseline to 5-weeks as measured by Personal Health Questionnaire (PHQ-8) (min: 0; max: 24, with higher score indicating more severe depression) for those with baseline PHQ-8 ≥10.

Original Primary Outcome Measures (submitted: August 20, 2020)

Change in depressive symptoms [ Time Frame: Change from Baseline to Post treatment (5 weeks) ]

Change in depressive symptoms measured by Personal Health Questionnaire (PHQ-8) (min: 0; max: 24, with higher score indicating more severe depression).

Current Secondary Outcome Measures (submitted: December 6, 2021)

• Phase I - Change in Depression Symptoms [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Between-subjects treatment-related change in depressive symptoms from baseline to 5-weeks as measured by Personal Health Questionnaire (PHQ-8) (min: 0; max: 24, with higher score indicating more severe depression) for those with baseline PHQ-8 ≥5. Only Phase I participants were included in this Outcome measure.
• Number of Participants in Remission [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Remission rates based on PHQ-8 < 10 (sub-analysis for those with baseline PHQ-8 ≥ 10). Phase I and Phase II participant arms are reported for this outcome.
• Change in Participant-rated Anxiety Symptoms and Global Functioning [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Between-subjects treatment-related change in participant-rated anxiety symptoms and global functioning as measured by GAD-7 Anxiety and PROMIS Pediatric Global Health Scale. The GAD-7 Anxiety is a brief 7-item assessment for generalized anxiety disorder. Values range from 0-21, with higher scores representing more severe anxiety. The PROMIS Pediatric Global Health Scale is a 7-item assessment for perceived physical, mental, and social health. Values range from 7-35, with higher scores representing better health. Phase I and Phase II participant arms are reported for this Outcome. Statistical Analyses are presented for Phase II results only because Phase I was intentionally not powered for analysis.
• Change in Parent-reported Depressive Symptoms and Global Functioning. [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Between-subjects treatment-related change in parent-reported depressive symptoms and global functioning as measured by Mood and Feelings Questionnaire (MFQ-PS), and PROMIS Parent Proxy Global Health Scale. The MFQ-PS consists of a series of 13 descriptive phrases regarding how the subject has been feeling or acting in the past two weeks and is a screening tool for depression in children and young people. Values range from 0-26, with higher scores representing more severe symptoms. The PROMIS Parent Proxy Global Health Scale is a 7-item assessment for perceived physical, mental, and social health. Values range from 7-35, with higher scores representing better health. Phase I and Phase II participant arms are reported for this Outcome. Statistical Analyses are presented for Phase II results only because Phase I was intentionally not powered for analysis.
• Average Treatment-related Usability and Engagement Ratings [ Time Frame: Post-Treatment ]
  Average treatment-related usability (System Usability Scale; SUS) and engagement (User Engagement Scale-Short Form; UES-SF) ratings. Phase I and Phase II participant arms are reported for this outcome. The SUS is a 10-item questionnaire measuring the usability of systems. Responses range from Strongly Agree to Strongly Disagree. Scores are percentile rankings and range from 0-100. Higher scores represent higher usability. The UES-SF is a 12-item questionnaire measuring self-reported user-engagement. The form uses a 5-point Likert scale. Overall engagement scores range from 1-5. Higher scores represent more engagement.
• Phase II - Safety [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Between-group treatment-related differences in clinical concern rates and serious clinical concerns. Phase II participant arms are reported for this outcome.
• App Engagement and Adherence [ Time Frame: From Baseline to Post Treatment (Week 5) ]
  Between-group treatment-related differences in program adherence and engagement based on behavioral and mobile app analytics. Phase I and Phase II Spark participant arms are reported for this outcome. We are reporting the average number of app modules completed (out of 5 total modules).

Original Secondary Outcome Measures (submitted: August 20, 2020)

• Change in anxiety symptoms [ Time Frame: Change from Baseline to Post treatment (5 weeks) ]
  Change in anxiety symptoms measured by the Generalized Anxiety Disorder (GAD-7) scale (min: 0; max: 21, with higher score indicating more severe anxiety).
• Change in parent report of child depressive symptoms [ Time Frame: Change from Baseline to Post treatment (5 weeks) ]
  Change in parent report of child depressive symptoms measured by the Mood and Feelings Questionnaire (MFQ) (min: 0; max: 26, with higher score indicating more severe depression)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A CBT-based Mobile Intervention as First Line Treatment for Adolescent Depression During COVID-19
• Official Title: Limbix Spark: A CBT-based Mobile Intervention as First Line Treatment for Adolescent Depression During COVID-19
• Brief Summary: Over 3 million teenagers in the USA have depression, and rates of depression and suicide are sharply increasing. Teenage depression has far-reaching consequences including impairments in academic and work performance and social and family relationships, substance abuse, and worsening of other health conditions, which can persist into adulthood. Access to mental health care for teenagers is limited due to a shortage of mental health providers and many teenagers and parents are reluctant to take antidepressants. COVID-19 and mandated physical and social distancing is expected to increase rates of teenage depression, and further limit access to traditional methods of care (e.g. psychotherapy). This highlights an urgent need to develop accessible, digital treatments for teenage depression to address the serious mental health impacts of the COVID-19 pandemic. This fully virtual study (https://www.limbix.com/spark) will compare the relative safety, effectiveness, and engagement of a mobile application based on cognitive behavioral therapy and behavioral activation (Limbix Spark), focusing on the idea that engaging in behaviors that are rewarding or provide a sense of mastery can be effective in reducing symptoms of depression. Limbix Spark will be compared to a mobile app containing educational material about depression (Psychoeducation).

Detailed Description

Depression in adolescence is a public health crisis, with incidence and suicide rates rising sharply over the past decade. The COVID-19 global pandemic, along with mandated social and physical distancing, is expected to have substantial repercussions on public mental health and exacerbate the mental health crisis among teens. Adolescents, a group with significant unmet mental health needs, are at risk during this time, as they are especially vulnerable to depression and suicidality following environmental stressors, trauma, and social isolation that are endemic to this global pandemic. With difficulties in receiving in person care magnified during social distancing, now more than ever, there is an immediate need for safe, accessible, and effective digital treatments for mental health disorders.

The proposed intervention is intended to increase access to mental health care during the COVID-19 pandemic. This study aims to evaluate the clinical effectiveness and safety of a cognitive behavioral therapy (CBT)- based digital treatment for adolescent depression (Limbix Spark) relative to psychoeducation. Limbix Spark implements behavioral activation (BA), a key CBT skill that provides a sense of pleasure or mastery through self-monitored activities to reduce depressive symptoms and improve functional outcomes.

Adolescents with depression (13-21 years old) across the country will be recruited to participate in a fully remote, clinical trial via https://www.limbix.com/spark. At an initial virtual visit, following informed consent, adolescents and parents (for those under 18) will fill out standardized questionnaires designed to measure symptoms of depression, anxiety, and general health. Participants will then download an app onto their mobile phone and be randomly assigned to one of two groups. One group will receive the Limbix Spark program and the other will receive the Psychoeducation program for 5 weeks. The Limbix Spark program is divided into 5 levels. Each level provides educational information about cognitive behavioral therapy and behavioral activation, and interactive activities including mood tracking and activity scheduling. The Psychoeducation program is divided into 5 lessons. Each lesson covers a different topic about depression. During both 5 week programs, patients will also complete a weekly Patient Health Questionnaire, which is designed to measure depressive symptoms and also will report any negative side effects they may be experiencing. After 5 weeks, participants and legal guardians (for those under 18) will complete another set of standardized questionnaires designed to measure symptoms of depression, anxiety, and general health. Patients will also complete questionnaires asking them about their thoughts and experiences with the program they just completed. Lastly, a subset of patients and parents will be invited to complete a virtual interview to provide feedback on using the program.

The trial will be divided into two phases. The first phase will enroll 60 participants and participants will be randomized to either Spark and Control groups as described above. The second phase will enroll 175 participants and those randomized into the control group will be given access to the 5-week Spark intervention after completing the 5 weeks of control condition (control extension arm). Once completing the control extension arm, participants will complete a second set of post study questionnaires after 5 weeks.

All study participants that complete the 5-week Limbix Spark program and the post study questionnaires will be contacted and asked to consent to participation in the follow-up study. Only participants who did not opt-out to being contacted for future research will be contacted. This study will collect questionnaires from participants at any or all of the following time frames as indicated: 1-month, 3-month, and 6-month following completion of the Spark arm.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Depression

Intervention

• Device: Limbix Spark
  The Limbix Spark program is divided into 5 levels. Each level provides educational information about cognitive behavioral therapy and interactive activities.
• Other: Psychoeducation
  The Psychoeducation program is divided into 5 lessons. Each lesson covers a different topic about depression.

Study Arms

• Experimental: Limbix Spark
  A 5 week CBT-based intervention
  Intervention: Device: Limbix Spark
• Active Comparator: Psychoeducation
  5 weeks of psychoeducation about depression. Upon completion, participants will be automatically enrolled into the Limbix Spark CBT-based intervention
  Intervention: Other: Psychoeducation

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 9, 2021): 227
• Original Estimated Enrollment (submitted: August 20, 2020): 410
• Actual Study Completion Date: January 16, 2022
• Actual Primary Completion Date: September 3, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Between the ages of 13 and 21
• Self-reported symptoms of depression
• Will be residing in the USA for the duration of the 5-week study
• Under the care of a US-based primary care and/or licensed mental healthcare provider and willing and able to provide the name and contact information of the provider during consent appointment.
• English fluency and literacy of adolescent and consenting legal guardian if under 18
• Access to a smartphone (iPhone 5s or later or running Android 4.4 KitKat or later) and regular internet access
• Willing to provide informed e-consent/assent and have legal guardian willing to provide informed e-consent if under 18.

Exclusion Criteria:

• Self-reported lifetime suicide attempt or active self-harm or active suicidal ideation with intent
• Have a diagnosis by a clinician of bipolar disorder, substance use disorder, or any psychotic disorder including schizophrenia
• Incapable of understanding or completing study procedures and digital intervention as determined by participant, patient/legal guardian, healthcare provider, or clinical research team

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Years to 21 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04524598
• Other Study ID Numbers: Limbix Spark 02
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Limbix Health, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Limbix Health, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jessica Lake, PhD; Director of Research
• Principal Investigator: Aarthi Padmanabhan, Phd; Research Director

• PRS Account: Limbix Health, Inc.
• Verification Date: July 2022